NeuroAIDS in India Viral and host factors, as well as comorbidities, play key roles in determining susceptibility to the neurologic complications associated with HIV infection. Most studies of HIV-related neurocognitive impairment have been conducted in Western countries, where HIV clade B predominates. Worldwide, however, clade C is much more common and recent virologic studies suggest that its neurovirulence may differ from clade B. Approximately 5 million individuals are infected with HIV in India, the vast majority with clade C virus. In the present study we will address the following aims within an Indian cohort: 1) to determine the prevalence and nature of HIV-associated neurocognitive impairment (HNCI) in HIV-infected individuals who are not on antiretroviral (ARV) therapy, 2) to determine the impact of newly-initiated ARV treatment on cognitive functioning, 3) to assess the viral (env, tat) genetics associated with HNCI, and 4) to determine the relationship between HNCI and host immunogenetic factors (i.e., genotype MCP-1, CCL3L1 copy number, RANTES and polymorphisms in CCR5/CCR2 to define CCR5 haplotypes). Building upon collaboration between the HIV Neurobehavioral Research Center (HNRC) in the U.S. and the National AIDS Research Institute (NARI) in Pune, India, we propose to examine 300 HIV+ individuals prior to initiation of ARVs in linked studies (HPTN 052, India National AIDS Control Organization program) and follow them annually thereafter. We will also enroll an HIV seronegative comparison group in order to establish neuropsychological norms for determining impairment in individual HIV+ persons. The feasibility of this study has been demonstrated by a pilot study in which we created Marathi-translated instruments, trained India personnel, and examined 60 participants using methods originally developed at the HNRC but adapted to India. This project will potentially a) lead to improved understanding of the characteristics and correlates of neurologic complications of clade C HIV infection in India and b) enhance existing clinical and scientific expertise in India via technology transfer in the areas of cognitive assessments, genomics, and biomarker assays.